Phosphoinositide 3-kinases (PI3Ks) are central regulators of cellular signalling, controlling cell survival, growth and metabolism. Each isoform has its own tissue distribution, functional role and regulatory mechanism. Our research asks what individual PI3K isoforms actually do, and how those roles change during cancer initiation and progression.
A major focus is the set of activating oncogenic mutations in the pathway that drive tumourigenesis across a wide range of cancers. By working out how these mutations promote uncontrolled proliferation and survival, we aim to identify isoform-selective therapeutic targets that could lead to more effective and less toxic treatment. The work also maps interactions between PI3K and other signalling pathways, which is where much of the complexity of tumour behaviour and therapy resistance lives.